title: Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel with concurrent thoracic irradiation in patients with malignant pleural mesothelioma and locally advanced non-small-cell lung cancer (NSCLC) using a 120-hour continuous infusion regimen. A secondary objective was to assess the effect of paclitaxel on the cell cycle through serial tumor biopsies.
  
  
  METHODS
  Paclitaxel was administered as a 120-hour (5-day) continuous infusion repeated every 3 weeks during the course of radiation therapy. The starting dose of paclitaxel was 90 mg/m2. Doses were escalated at 15-mg/m2 increments in successive cohorts of three patients. In NSCLC patients, radiation was delivered to the primary tumor and regional lymph nodes for a total tumor dose of 6,120 cGy. In mesothelioma patients, hemithoracic irradiation was delivered as the initial treatment field with a conedown to the tumor volume for a total dose of 5,760 to 6,300 cGy. Tumor biopsies were obtained, if possible, before and during paclitaxel treatment.
  
  
  RESULTS
  Thirty patients were entered onto this study through three dose levels (from 90 mg/m2 to 120 mg/m2). The MTD was determined to be 105 mg/m2. The dose-limiting toxicity was grade 4 neutropenia (two patients). Grade 2 gastrointestinal (GI) toxicity (nausea and vomiting) was also observed at 120 mg/m2. Three of 30 patients developed a hypersensitivity reaction. Six patients had grade 2 lung injury manifested by a persistent cough that required antitussives. Five patients underwent tumor biopsies. None of the patients showed a significant block of cells in mitosis (G2/M) after paclitaxel infusion.
  
  
  CONCLUSIONS
  The MTD of paclitaxel, when administered as a 120-hour continuous infusion with concurrent radiotherapy, was determined to be 105 mg/m2. The dose-limiting toxicity was neutropenia. Continuous infusion paclitaxel administered with large field irradiation of the lung is well tolerated and deserves continued evaluation.
authors.affiliation: Radiation Oncology Branch, Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892, USA. herscher@box-h.nih.gov
authors.forename: L L
authors.initials: LL
authors.lastname: Herscher
authors.forename: S M
authors.initials: SM
authors.lastname: Hahn
authors.forename: G
authors.initials: G
authors.lastname: Kroog
authors.forename: H
authors.initials: H
authors.lastname: Pass
authors.forename: B
authors.initials: B
authors.lastname: Temeck
authors.forename: B
authors.initials: B
authors.lastname: Goldspiel
authors.forename: J
authors.initials: J
authors.lastname: Cook
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: J
authors.initials: J
authors.lastname: Liebmann
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008654:Mesothelioma / Q000532:radiotherapy*; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage
chemical_list: D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel